Effects of the Mixed Mu/Kappa Opioid Nalbuphine on Cocaine-Induced Changes in Subjective and Cardiovascular Responses in Men

  title={Effects of the Mixed Mu/Kappa Opioid Nalbuphine on Cocaine-Induced Changes in Subjective and Cardiovascular Responses in Men},
  author={Nancy K. Mello and Jack H. Mendelson and Michelle B. Sholar and Maria Jaszyna-Gasior and Nathalie V. Goletiani and Arthur J. Siegel},
Kappa opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and reduce cocaine self-administration by rhesus monkeys. We compared the cardiovascular and subjective effects of acute doses of the mu/kappa opioid nalbuphine alone (5 mg/70 kg, intravenous (i.v.)), with cocaine alone (0.2 mg/kg, i.v.), and with nalbuphine+cocaine in combination, under placebo-controlled, double-blind conditions. Subjects met American Psychiatric Association Diagnostic and… 

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

The mu/kappa agonist nalbuphine attenuates sensitization to the behavioral effects of cocaine

Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers

Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour

ITA1003 showed less motor suppression than morphine in both acute and sub-chronic treatment regimens, while it did not affect morphine-induced motor suppression or hyper-excitation, and it is speculated that UTA1003 crosses the blood-brain barrier after subcutaneous administration and, therefore, could be developed as a lead molecule to avoid opioid-induced antinociceptive tolerance and motor suppression.

Investigating the anti-cocaine, anti-nociceptive properties and side effects of MP1104, a novel mixed opioid receptor agonist

MP1104, a potent mixed opioid receptor agonist, with full efficacy at all three receptors and 3- and 13-fold higher binding affinity for KOPr compared to MOPr and DOPr, is evaluated for the ability to modulate cocaine-induced behaviours, the anti-nociceptive effects and side effects.

Effects of ATPM-ET, a novel κ agonist with partial μ activity, on physical dependence and behavior sensitization in mice

ATPM-ET may have potential as a therapeutic agent for the treatment of drug abuse and in the hot plate test, it produced a dose-dependent antinociceptive effect.

MDMA (“ecstasy”) abuse as an example of dopamine neuroplasticity

  • S. Schenk
  • Psychology, Biology
    Neuroscience & Biobehavioral Reviews
  • 2011

Multifunctional Opioid Ligands.

This chapter describes several classes of multifunctional ligands that interact with at least one opioid receptor and the structures, pharmacological utility, and therapeutic drawbacks of these classes of ligands are discussed.



Effects of mixed-action kappa/mu opioids on cocaine self-administration and cocaine discrimination by rhesus monkeys.

Kappa and mixed kappa/mu-opioid agonists may reduce cocaine self-administration without altering cocaine's discriminative stimulus effects.

Effects of kappa opioids on cocaine self-administration by rhesus monkeys.

It is shown that chronic administration of EKC and U50,588 produce a dose-dependent, kappa receptor-mediated and often sustained decrease in cocaine self-administration, which may complicate their use as treatments for cocaine dependence.

Effects of Mixed-Action κ/μ Opioids on Cocaine Self-Administration and Cocaine Discrimination by Rhesus Monkeys

Mixed κ/μ agonists appear to offer some advantages over selective κ agonists as potential treatments for cocaine abuse and may reduce cocaine self-administration without altering cocaine's discriminative stimulus effects.

Effects of kappa opioid agonists on cocaine- and food-maintained responding by rhesus monkeys.

  • N. MelloS. Negus
  • Biology, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1998
It is suggested that kappa opioid agonists may be a useful approach to the development of new pharmacological treatments for cocaine dependence and undesirable side effects may limit their clinical usefulness.

The Effects of Nalbuphine and Butorphanol Treatment on Cocaine and Food Self-Administration by Rhesus Monkeys

It is suggested that these opioid mixed agonist-antagonist analgesics may not be useful as pharmacotherapies for the treatment of cocaine abuse.

Enadoline and butorphanol: evaluation of kappa-agonists on cocaine pharmacodynamics and cocaine self-administration in humans.

The data suggest that these kappa-agonists may be safely administered in the presence of cocaine but do not produce significant attenuation of cocaine's direct effects or self-administration under these acute dosing conditions.

Effects of μ-Opioid Agonists on Cocaine- and Food-Maintained Responding and Cocaine Discrimination in Rhesus Monkeys: Role of μ-Agonist Efficacy

It is suggested that low-efficacy mu-agonists may decrease cocaine self-administration to a greater degree and with fewer undesirable effects than high-efficiency mu-agonist agonists.

Kappa opioid inhibition of morphine and cocaine self-administration in rats

Antagonist effects of nalbuphine in opioid-dependent human volunteers.

Nalbuphine produced effects which were qualitatively similar to the effects of naloxone and showed no evidence of opioid agonist effects in these methadone-dependent subjects and the withdrawal syndrome precipitated by nal Buphine was indistinguishable from that produced by n aloxone.